Recombinant Tissue Plasminogen Activator-conjugated Nanoparticles Effectively Targets Thrombolysis in a Rat Model of Middle Cerebral Artery Occlusion

Summary The efficacy and safety of recombinant tissue plasminogen activator (rtPA) need to be improved due to its low bioavailability and requirement of large dose administration. The purpose of this study was to develop a fibrin-targeted nanoparticle (NP) drug delivery system for thrombosis combina...

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Bibliographic Details
Published in:Current medical science 2018-06, Vol.38 (3), p.427-435
Main Authors: Deng, Jun, Mei, Heng, Shi, Wei, Pang, Zhi-qing, Zhang, Bo, Guo, Tao, Wang, Hua-fang, Jiang, Xin-guo, Hu, Yu
Format: Article
Language:English
Subjects:
Medicine
Medicine & Public Health
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Summary:Summary The efficacy and safety of recombinant tissue plasminogen activator (rtPA) need to be improved due to its low bioavailability and requirement of large dose administration. The purpose of this study was to develop a fibrin-targeted nanoparticle (NP) drug delivery system for thrombosis combination therapy. We conjugated rtPA to poly(ethylene glycol)- poly(e-caprolactone) (PEG-PCL) nanoparticles (rtPA-NP) and investigated its physicochemical characteristics such as particle size, zeta potential, enzyme activity of conjugated rtPA and its storage stability at 4°C. The thrombolytic activity of rtPA-NP was evaluated in vitro and in vivo as well as the half-life of rtPA-NP, the properties to fibrin targeting and its influences on systemic hemostasis in vivo . The results showed that rtPA-NP equivalent to 10% of a typical dose of rtPA could dissolve fibrin clots and were demonstrated to have a neuroprotective effect after focal cerebral ischemia as evidenced by decreased infarct volume and improved neurological deficit ( P
ISSN:2096-5230
2523-899X
DOI:10.1007/s11596-018-1896-z